Institoris E
Chem Biol Interact. 1981 May;35(2):207-16. doi: 10.1016/0009-2797(81)90144-7.
In vivo alkylation of Yoshida sarcoma cell DNA by 3H-labelled 1,2:5,6-dianhydrogalactitol (DAG) yielded N-7 monogalactitylguanines and 1,6-di-(guanin-7-yl)-galactitol, similar to the alkylated products obtained by in vitro reaction of DNA with dianhydrogalactitol in neutral solution. The ratio between monoalkylguanines and diguaninyl product was 2-2.5, slightly increasing with doses. Persistence of alkylated products in DNA was followed in function of time. There was no significant loss of either monoalkylated bases or diguaninyl derivative during the observation period i.e. 7-24 h after treatment. In contrast, the physical measurements of the amount of renaturable DNA showed a rapid opening of cross-links in the same period. Taking the presence of diguaninyl moiety as an indicator of cross-links in DNA, these two latter findings show an apparent contradiction which could be reconciled however by the mechanism proposed by Reid and Walker (Biochim. Biophys. Acta, 179 (1969) 179) for the removal of cross-linkage induced by HN2. Accordingly, one arm of the cross-links is removed, probably enzymically, leaving the DNA non-renaturable, while the other arm of cross-link is still covalently attached to the DNA molecule rendering possible the detection of diguaninyl moiety in DNA at some later time. This concept for the removal of cross-links from DNA seems to be supported by our results too.
用³H标记的1,2:5,6 - 二脱水半乳糖醇（DAG）对吉田肉瘤细胞DNA进行体内烷基化反应，产生了N - 7单半乳糖基鸟嘌呤和1,6 - 二 -（鸟嘌呤 - 7 - 基）- 半乳糖醇，这与DNA在中性溶液中与二脱水半乳糖醇进行体外反应所得到的烷基化产物相似。单烷基鸟嘌呤与双鸟嘌呤基产物之间的比例为2 - 2.5，随剂量略有增加。随着时间的推移追踪了DNA中烷基化产物的持久性。在观察期内，即处理后7 - 24小时，单烷基化碱基或双鸟嘌呤基衍生物均无明显损失。相比之下，对可复性DNA量的物理测量表明，在同一时期交联迅速打开。以后者双鸟嘌呤基部分的存在作为DNA中交联的指标，这后两个发现显示出明显的矛盾，然而通过Reid和Walker（《生物化学与生物物理学报》，179 (1969) 179）提出的关于去除由HN2诱导的交联的机制可以得到解释。因此，交联的一个臂可能通过酶促作用被去除，使DNA不可复性，而交联的另一个臂仍共价连接在DNA分子上，使得在稍后的某个时间能够检测到DNA中的双鸟嘌呤基部分。从DNA中去除交联的这一概念似乎也得到了我们结果的支持。
